It is less solvated, and hence much more reactive, in alcohol solvents, and in pure DMSO its reactivity is increased by some twelve orders of magnitude. Enough kinetic evidence to prove or disprove this probably exists, and work to do this is underway. The scheme is drawn this way in consequence of the observation that hydroxide ion does not add to carbonyl groups directly, but instead attacks a water molecule which does the actual addition. It is now well established that secondary substrates react by an S N2 process, for instance as shown in Scheme I, although for the example shown the specific mechanism given is still speculative. In some (but not all) textbooks one still sees mention of “mixed S N1 and S N2” mechanisms involving secondary substrates, due primarily to the early work of the Hughes and Ingold school, which has since been discredited.
It is now apparent that this is true of secondary carbocations too.
For instance, it is certain that primary carbocations cannot exist in a primarily aqueous medium, although mechanisms involving them are still occasionally proposed. However, more is known now, and although it is still not easy to apply, the author believes that much more attention has to be paid to what I might call the “Jencks Principle”. Jencks pointed this out a number of years ago now, as the concept of an “enforced mechanism” if a species cannot exist under the reaction conditions a mechanism involving it is impossible, and an alternate one is “enforced”.Īt the time Jencks wrote his review not a lot was known about the lifetimes of putative reaction intermediates. However, if a species is to be a reaction intermediate, it has to be stable enough to have a lifetime of at least a few molecular vibrations under the reaction conditions, say greater than 10 −13–10 −14 s. For instance, carbocations and other species have been studied extensively in superacid media by Olah and his colleagues. In recent years, the study of the mechanisms of organic reactions has been considerably enhanced by the study of putative reaction intermediates, often under conditions in which the species are stable enough for spectroscopic examination. The Grotthuss mechanism also means that reactions involving neutral water are favored the solvent is already highly structured, so the entropy involved in bringing several solvent molecules to the reaction center is unimportant. General acid catalysis is the rule in reactions in concentrated aqueous acids. Any charged oxygen species (e.g., a tetrahedral intermediate) is also not going to exist long enough to be a reaction intermediate, unless the charge is stabilized in some way, usually by resonance. Important mechanistic consequences result. Thanks to the Grotthuss mechanism of chain transfer along hydrogen bonds, in reality a proton or a hydroxide ion is simply instantly available anywhere it is needed for reaction.
The lifetime of any ionized water species is exceedingly short, a few molecular vibrations at most the best experimental study, using modern IR instrumentation, has the most probable hydrated proton structure as H 13O 6 +, but only an estimated quarter of the protons are present even in this form at any given instant. Several recent high-level calculations on large proton clusters are unable to localize the positive charge it is found to be simply “on the cluster” as a whole.
More importantly, it is now known that neither H 3O + nor HO − exist as such in dilute aqueous solution. Only tertiary carbocations and those stabilized by resonance (benzyl cations, acylium ions) are stable enough to be reaction intermediates. For instance, neither primary nor secondary carbocations have long enough lifetimes to exist in an aqueous medium, so S N1 reactions involving these substrates are not possible, and an S N2 mechanism is enforced. This principle was first enunciated by Jencks, as the concept of an enforced mechanism. If a species does not have a finite lifetime in the reaction medium, it cannot be a mechanistic intermediate.